2-Fluorohistidine but not the 4-fluoro isomer, is rapidly incorporated into newly synthesized animal or bacterial protein, in place of histidine. 2-Fluorohistidine also serves to produce leucopenia, temporary regression of the mouse spleen, thymus, lymph nodes, and hypocellularity of the bone marrow. In mice infected with leukemia virus P-388, this analog prevents the normally massive increase in leukocyte levels and increases survival time up to 50%. This antileukemic action may be unrelated to production of false protein, and may result from a block in the utilization of histidine as a one-Carbon donor in purine biosynthesis. The block would result from the powerful inhibition of urocanase by 2-fluorocanic acid, a metabolite of 2-fluorohistidine. A synthetic route to 2-fluorourocanic acid has now been developed. The same route will lead to the synthesis of 2,4-difluorohistidine, an analogue which may be even more effective than 2-fluorohistidine.